Department of Molecular Biology, Medical Biochemistry, and Pathology, Centre de Recherche en Cancérologie de l'Université Laval, Hôpital Hôtel-Dieu de Québec, Québec, Canada.
J Gerontol A Biol Sci Med Sci. 2011 Mar;66(3):264-78. doi: 10.1093/gerona/glq184. Epub 2010 Oct 25.
Werner syndrome is a premature aging disorder caused by mutations in a RecQ-like DNA helicase. Mice lacking the helicase domain of the WRN homologue exhibit many features of Werner syndrome, including a pro-oxidant status and a shorter mean life span. Here, we show that resveratrol supplementation improved the hyperglycemia and the insulin resistance phenotype in these Wrn mutant mice. In addition, resveratrol reversed liver steatosis, lipid peroxidaton, and the defenestration phenotypes observed in such mice. Resveratrol, however, did not improve the hypertriglyceridemia, inflammatory stress, nor extend the mean life span of these mutant mice. Microarray and biologic pathway enrichment analyses on liver tissues revealed that resveratrol mainly decreased lipidogenesis and increased genes involved in the insulin signaling pathway and the glutathione metabolism in Wrn mutant mice. Finally, resveratrol-treated mutant mice exhibited an increase in the frequency of lymphoma and of several solid tumors. These results indicate that resveratrol supplementation might exert at least metabolic benefits for Werner syndrome patients.
沃纳综合征是一种由 RecQ 样 DNA 解旋酶突变引起的过早衰老疾病。缺乏 WRN 同源物解旋酶结构域的小鼠表现出许多沃纳综合征的特征，包括氧化应激状态和平均寿命缩短。在这里，我们表明白藜芦醇补充改善了这些 Wrn 突变小鼠的高血糖和胰岛素抵抗表型。此外，白藜芦醇逆转了在这些小鼠中观察到的肝脂肪变性、脂质过氧化和窗格化表型。然而，白藜芦醇并没有改善这些突变小鼠的高甘油三酯血症、炎症应激，也没有延长它们的平均寿命。对肝组织的微阵列和生物途径富集分析表明，白藜芦醇主要降低了脂质生成，并增加了参与胰岛素信号通路和谷胱甘肽代谢的基因。最后，用白藜芦醇处理的突变小鼠淋巴瘤和几种实体瘤的发生率增加。这些结果表明，白藜芦醇补充可能至少为沃纳综合征患者带来代谢益处。
